Generation and Characterization of Murine Monoclonal Antibodies anti-PBP2a of Methicillin-resistant<i>Staphylococcus aureus</i>

Senna, José Procópio Moreno; Teixeira, Maria da Glória Martins; Santiago, Marta de Almeida; Batoreu, Nadia Maria; Valadares, Napoleão Fonseca; Galler, Ricardo

doi:10.1089/mab.2015.0013

Cited by 6 publications

(4 citation statements)

References 20 publications

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“…aureus [11], confirming the specificity of anti-PBP2a antibodies against MRSA. The MAb presented here was derived from this work, and it was obtained and characterized in previous studies [11,13,14]. We previously demonstrated that this MAb binds strongly to recombinant PBP2a and recognizes native PBP2a protein on the bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…Two studies employing DNA vaccination demonstrated that PBP2a generates an immune response and eliminates bacteria after systemic infection in immunized mice [11–12]. We recently reported the generation and characterization of murine MAbs that specifically bind PBP2a in vitro with high affinity [13]. In another study, we demonstrated that this anti-PBP2a antibody recognizes PBP2a protein on the bacterial surface using an immunofluorescence assay [14].…”

Section: Introductionmentioning

confidence: 99%

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Monoclonal antibody anti-PBP2a protects mice against MRSA (methicillin-resistant Staphylococcus aureus) infections

Saraiva

Araújo

et al. 2019

PLoS ONE

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Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant bacterium responsible for serious nosocomial and community-acquired infections worldwide. Since few antibiotics are effective for treating MRSA infections, the development of new therapies is of great importance. Previous studies demonstrated that PBP2a is a target that generates protective antibodies against MRSA. A murine monoclonal antibody (MAb) that recognizes PBP2a from MRSA strains was previously isolated and characterized. In this report, we evaluated the biodistribution of this MAb in blood and tissues, as well as the extent of protection conferred using prophylactic and therapeutic assays compared to vancomycin treatment. Biodistribution was evaluated 12–96 h after MAb administration. It predominantly remained in the serum, but it was also detectable in the kidneys, lungs, and spleen at low concentrations (about 4.5% in the kidneys, 1.9% in the lungs, and 0.7% the spleen) at all observed timepoints. Prophylactic studies in a murine model demonstrated a significant bacterial load reduction in the kidneys of the groups treated with either with IgG (greater than 3 logs) or F(ab’)2 (98%) when compared to that of the control groups (untreated). Mice were challenged with a lethal dose, and the survival rate was higher in the treated mice. Treatment with the MAb resulted in a bacterial load reduction in the kidneys similar to that of mice treated with vancomycin, and a MAb/vancomycin combination therapy was also effective. These results demonstrate that an anti-PBP2a MAb may be a promising therapeutic for treating MRSA infections.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Monoclonal antibody anti-PBP2a protects mice against MRSA (methicillin-resistant Staphylococcus aureus) infections

Saraiva

Araújo

et al. 2019

PLoS ONE

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“…Results obtained by Naghshbandi et al showed that passive immunization with rabbit purified polyclonal antibodies against recombinant PBP2a results in a significant increase in the survival rate of mice challenged with a lethal dose of MRSA and reduction of bacterial spread to the internal organs, confirming the potential importance of passive immunization with anti-PBP2a antibodies in controlling MRSA infections [ 81 ]. Monoclonal antibodies against PBP2a have also been generated and extensively characterized, but their efficacy in immunoprophylaxisis is still to be determined [ 82 , 83 ].…”

Section: Antibodies In Bacterial Infectionsmentioning

confidence: 99%

Antibody-Based Agents in the Management of Antibiotic-Resistant Staphylococcus aureus Diseases

2018

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Staphylococcus aureus is a human pathogen that can cause a wide spectrum of diseases, including sepsis, pneumonia, arthritis, and endocarditis. Ineffective treatment of a number of staphylococcal infections with antibiotics is due to the development and spread of antibiotic-resistant strains following decades of antibiotic usage. This has generated renewed interest within the scientific community in alternative therapeutic agents, such as anti-S. aureus antibodies. Although the role of antibodies in the management of S. aureus diseases is controversial, the success of this pathogen in neutralizing humoral immunity clearly indicates that antibodies offer the host extensive protection. In this review, we report an update on efforts to develop antibody-based agents, particularly monoclonal antibodies, and their therapeutic potential in the passive immunization approach to the treatment and prevention of S. aureus infections.

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“…[ 12 ] This causes the bacteria to lose resistance to beta‐lactam antibiotics because their cell walls can no longer effectively remain intact, ultimately leading to the death of the bacterium. [ 13 ] By blocking the function of PBP2a, anti‐PBP2a can inhibit the proliferation of MRSA and other PBP2a‐carrying bacteria.…”

Section: Introductionmentioning

confidence: 99%

It Takes Two to Tangle: Microneedle Patches Co‐delivering Monoclonal Antibodies and Engineered Antimicrobial Peptides Effectively Eradicate Wound Biofilms

Su,

Shahriar,

Andrabi

et al. 2024

Macromolecular Bioscience

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Wound biofilms pose a great clinical challenge. Herein, we report a dissolvable microneedle patch for dual delivery of monoclonal antibodies anti‐PBP2a and engineered antimicrobial peptides W379. in vitro antibacterial efficacy testing with microneedle patches containing a combination of 250 ng/mL W379 and 250 ng/mL anti‐BPB2a decreased the bacterial count from ∼3.31 × 107 CFU/mL to 1.28 × 102 CFU/mL within 2 h without eliciting evident cytotoxicity. ex vivo testing indicates W379 and anti‐PBP2a co‐loaded microneedle patch displayed a remarkable reduction of bacterial load by approximately 7.18 log CFU after administered only once within 48 h. The bacterial count was significantly diminished compared to the treatment by either W379 or anti‐PBP2a‐loaded alone microneedle patches. When administered twice within 48 h, no bacteria were identified. Further in vivo study also revealed that after two treatments of W379 and anti‐PBP2a co‐loaded PVP microneedle patches within 48 h, the bacterial colonies were undetectable in a type II diabetic mouse wound biofilm model. Taken together, W379 and anti‐PBP2a co‐loaded PVP microneedle patches hold great promise in treating wound biofilms.This article is protected by copyright. All rights reserved

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Generation and Characterization of Murine Monoclonal Antibodies anti-PBP2a of Methicillin-resistantStaphylococcus aureus

Cited by 6 publications

References 20 publications

Monoclonal antibody anti-PBP2a protects mice against MRSA (methicillin-resistant Staphylococcus aureus) infections

Monoclonal antibody anti-PBP2a protects mice against MRSA (methicillin-resistant Staphylococcus aureus) infections

Antibody-Based Agents in the Management of Antibiotic-Resistant Staphylococcus aureus Diseases

It Takes Two to Tangle: Microneedle Patches Co‐delivering Monoclonal Antibodies and Engineered Antimicrobial Peptides Effectively Eradicate Wound Biofilms

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